Establishment of RWS guidance reflecting contributions of China to regulatory science.

China's accession to the ICH has accelerated the advancement of its regulatory science. To foster innovation and improve the efficiency of pharmaceutical research and development, the China National Medical Products Administration (NMPA) encourages the use of real-world evidence (RWE) to support drug regulatory decision-making and has constructed a series of real-world study (RWS) related guidance, reflecting the contribution of the NMPA to the field of RWS in drug clinical development. Based on the four guidelines on RWE, real-world data (RWD), RWS design and protocol development, and communication with regulatory authorities, the guidance has been extended to more specific clinical applications, such as oncology, rare diseases, pediatric drugs, and traditional Chinese medicine. This paper reviews the core content and features of the series of RWS guidelines, presents their role in promoting drug development, and discusses challenges of using RWE in support of drug regulatory decision-making in China.

Prevalence of chronic hepatitis B and status of HBV care among rural women who planned to conceive in China.

Globally, one third of prevalent chronic hepatitis B (CHB) virus infection (HBV) occurred in China. Assessing the prevalence of CHB infesction and status of HBV-related services among pre-conception women will provide insight into risks of mother to child transmission (MTCT). A cross-sectional analysis of data from the National Free Pre-pregnancy Checkups (NFPC) program in 2010-2014 was conducted. A standardized questionnaire which collected demographic information and enzyme-linked immunosorbent assays (ELISA) which tested serological HBV markers were applied. A total of 16,051,850 rural women aged 15-49 years were included. 5.2% of women were infected with CHB, among whom, 28.6% were also hepatitis B e antigen (HBeAg) positive. The most CHB concentrated places were distributed in southeastern coastal provinces. Women born after 1992 did not experience a higher level of vaccine-induced immunity compared to those born before 1992. Nine in ten rural women with CHB were not aware of their HBV status and a very small proportion of women (0.22%) had received antiviral treatment. Our data demonstrated an overall high-intermediate burden of CHB. Heterogeneity of geographic distribution, high proportion of HBeAg, insufficient awareness of HBV status, and low access to HBV treatment are challenges for preventing the MTCT.

Association of Husband Smoking With Wife's Hypertension Status in Over 5 Million Chinese Females Aged 20 to 49 Years.

BACKGROUND: The effect of second-hand smoking, especially husband smoking, on wife's hypertension has not been well studied. The current study was aimed to assess the association of husband smoking with wife's hypertension among females aged 20 to 49 years. METHODS AND RESULTS: This study included 5 027 731 females along with their husbands from the National Free Pre-pregnancy Checkup Projects conducted across 31 provinces in China in 2014. Smoking/passive smoking status was collected by a standard questionnaire and blood pressure was measured by an electronic device after 10 minutes rest. Odds ratios and their corresponding 95% CIs for female hypertension were estimated according to smoking status of husband and wife, husbands' smoking amount, and cumulative exposure to husband smoking. Compared with neither-smoker group, the multivariable-adjusted odds ratio for female hypertension was 1.28 (1.27-1.30), 1.53 (1.30-1.79), and 1.50 (1.36-1.67) in husband-only, wife-only, and mixed group, respectively. Furthermore, a higher risk of having hypertension was associated with amount and cumulative exposure of husband smoking. For example, compared with neither-smoker, the multivariate-adjusted odds ratio was 1.22 (1.19-1.25), 1.24 (1.21-1.26), 1.32 (1.26-1.37), 1.37 (1.34-1.41), and 1.75 (1.64-1.87) for females whose husband smoked 1 to 5, 6 to 10, 11 to 15, 16 to 20, and ≥21 cigarettes per day, respectively (Pfor trend<0.001). Subgroup analyses identified similar results. CONCLUSIONS: There were associations of husband smoking with female hypertension prevalence. A family-based smoking restriction strategy may reduce smoking in males and improve hypertension control in females.

Status of HBsAg seroprevalence in 15 million rural couples in China: a cross-sectional study.

A cross-sectional analysis of prevalence of hepatitis B virus infection (HBV) among rural couples was conducted between 2010 and 2014. Serologic HBV markers, including hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), were tested. Primary outcome of interest comprised HBsAg positivity in couples (both positive: F+M+, only wife positive: F+M-, only husband positive: F-M+), and secondary outcome consisted of prevalence and risk factors of HBsAg positivity among husbands or wives. Of 14,816,300 couples included, 0.7% were F+M+; 6.3% were F-M+; 4.4% were F+M-, resulting in the overall seroprevalence of 11.4%. Individually, 6.1% were HBsAg positive with a higher rate seen in husbands (7.0%) than in wives (5.2%). Wife's HBeAg(+)/HBsAg (+) (AOR = 2.61), HBeAg(-)/HBsAg (+) (AOR = 2.23), positivity of syphilis (AOR = 1.50), living in a high-risk region (AOR = 1.46) were significantly predictors of HBsAg positivity in husbands. Prevalence and predictors of HBsAg positivity in wives had similar results. Our data show a high burden and discordant pattern of HBV infection in rural couples, and partner's double positivity of HBeAg and HBsAg was the most significant factor of HBV infection in couples. A comprehensive strategy that emphasizes vaccination and education is needed.

Effect of folic acid supplementation on preterm delivery and small for gestational age births: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of folic acid (FA) supplementation on the risks of preterm delivery (PTD) and small for gestational age births (SGA). DATA SOURCES: Cohort studies were identified from MEDLINE, EMBASE, the Cochrane Library, CINAHL, and CBM from inception to January 2015. PARTICIPANTS AND INCLUDED STUDIES: Healthy women who want to get pregnancy or being pregnant. MAIN OUTCOME MEASURES: PTD and SGA. RESULTS: The association of FA and PTD was significant when supplement initiated after pregnancy (RR=0.68, 95%CI, 0.52-0.90), whereas no effect was founded if the initiation time was before conception (RR=0.89, 95%CI, 0.80-1.01). The results for the association between FA supplementation and SGA showed significant protective effect: initiated before conception (RR=0.70, 95%CI, 0.57-0.85) and initiated after conception (RR=0.84, 95%CI, 0.81-0.89). CONCLUSION: Folic acid supplementation is associated with a significant reduction on the risk of PTD when initiated after conception. It can also protect fetus from SGA.

Seroepidemiological survey of hepatitis B virus infection among 764,460 women of childbearing age in rural China: A cross-sectional study.

BACKGROUND: China has historically been a highly endemic area for hepatitis B infection. Progress has been made in tackling the disease in infants and children, but infection rates remain high in adults, especially in rural areas. Current data on the prevalence of HBV in women of childbearing age is lacking. OBJECTIVES: We analyzed the HBV serological status of women of childbearing age in rural China to provide data to inform the development of prevention and control measures for hepatitis B. STUDY DESIGN: Questionnaires and serum samples have been collected from rural couples aged 20-49 years in 292 counties in 2014. ELISA methods were employed to detect serum HBV markers. RESULTS: From January to December 2014, 771,567 questionnaires and 764,460 blood samples were collected. Among these, 44,057 (5.76%) women tested positive for HBsAg and 100,519 (13.24%) tested positive for anti-HBc. In this sub group, 39,862 (39.66%) women also tested positive for HBsAg. There were 338,528 (41.67%) tested positive for anti-HBs and single anti-HBs presented in 259,800 (33.98%) women. In total, 385,140 (50.38%) tested negative for all HBV markers. Of the HBsAg positive participants, 12,520 (28.42%) were positive for both HBsAg and HBeAg, and therefore infectious although this declined with age (P<0.001). Prevalence of HBsAg positivity was highest in the 'eastern' region (P<0.001). CONCLUSIONS: HBV prevalence among women of childbearing age in rural China has declined compared to the 2006 National study of women aged 15-59 years (5.76 vs. 6.73%), but remains high.

Folic acid supplementation, preconception body mass index, and preterm delivery: findings from the preconception cohort data in a Chinese rural population.

BACKGROUND: Folic acid (FA) supplementation before and during the first trimester can reduce the risk of occurrence of preterm delivery (PTD). Preconception body mass index (BMI) is also associated with PTD. This study aimed to investigate the combined effect of FA supplements and preconception BMI on the risk of PTD. METHODS: The data of a cohort from 2010-2011 that was obtained through a preconception care service in China was used (including 172,206 women). A multivariable regression model was used to investigate the association between maternal preconception conditions and the risk of PTD. The interaction of preconception BMI and FA supplementation was measured by a logistic regression model. RESULTS: Taking FA supplements in the preconception period or in the first trimester reduced the risk of PTD (odds ratio [OR] = 0.58 and OR = 0.61, respectively). Women with an abnormal BMI had an increased risk of PTD (OR = 1.09, OR = 1.10, and OR = 1.17 for underweight, overweight, and obese, respectively). Preconception BMI showed an interaction with the protective effect of FA supplementation for PTD. With regard to the interaction of FA supplementation, the adjusted odds ratio (aOR) was 0.57 (95% CI: 0.51, 0.64) in underweight women, 0.85 (95% CI: 0.73, 0.98) in overweight women, and 0.77 (95% CI, 0.65, 0.91) in obese women. Preconception BMI also showed an interaction with the time of FA supplementation. Women with a normal BMI who began to take FA supplements in the preconception period had the lowest risk of PTD (aORs: 0.58 vs. 0.65 beginning in the first trimester). The aORs at preconception and the first trimester in the underweight group were 0.56 vs. 0.60. The aORs at preconception and the first trimester were 0.94 vs. 0.65 and 1.15 vs. 0.60 in the overweight and obesity groups, respectively. CONCLUSIONS: In our study, FA supplements reduced the risk of PTD, while abnormal BMI raised the risk of PTD, although higher BMI categories did not have this higher risk once adjusted analysis was conducted. The protective effect of FA supplementation for PTD was reduced in women with overweight or obesity. To get better protection of FA supplementation, women with normal BMI or underweight should begin to use in preconception, while women with overweight or obesity should begin to use after conception.